• Title/Summary/Keyword: molecular pathogenesis

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Various Classification of Gastric Adenocarcinoma

  • Moon, Hee Seok;Jeong, Hyun Yong
    • Journal of Digestive Cancer Reports
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    • v.7 no.1
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    • pp.8-12
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    • 2019
  • Despite its declining incidence, gastric cancer is globally, still, the third most common cause of cancer-related mortality. Gastric cancer is a heterogeneous disease with diverse pathogenesis and molecular backgrounds. Therefore several systems have been proposed to aid in the classification of gastric adenocarcinoma based on the macroscopic, microscopic and anatomical features of the tumor. However, these classifications did not reflect the pathogenesis of the disease. Recently, genomic analysis has identified several subtypes of gastric adenocarcinoma and a detailed understanding of the molecular biology behind the neoplastic phenotype is possible to develop of more effective therapies. We will describe the existing various classification of gastric cancer and the recently introduced molecular biology and immunological classification.

New Insights into the Role of E2s in the Pathogenesis of Diseases: Lessons Learned from UBE2O

  • Hormaechea-Agulla, Daniel;Kim, Youngjo;Song, Min Sup;Song, Su Jung
    • Molecules and Cells
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    • v.41 no.3
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    • pp.168-178
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    • 2018
  • Intracellular communication via ubiquitin (Ub) signaling impacts all aspects of cell biology and regulates pathways critical to human development and viability; therefore aberrations or defects in Ub signaling can contribute to the pathogenesis of human diseases. Ubiquitination consists of the addition of Ub to a substrate protein via coordinated action of E1-activating, E2-conjugating and E3-ligating enzymes. Approximately 40 E2s have been identified in humans, and most are thought to be involved in Ub transfer; although little information is available regarding the majority of them, emerging evidence has highlighted their importance to human health and disease. In this review, we focus on recent insights into the pathogenetic roles of E2s (particularly the ubiquitin-conjugating enzyme E2O [UBE2O]) in debilitating diseases and cancer, and discuss the tantalizing prospect that E2s may someday serve as potential therapeutic targets for human diseases.

Occurrence of dsRNA Mycovirus (LeV-FMRI0339) in the Edible Mushroom Lentinula edodes and Meiotic Stability of LeV-FMRI0339 among Monokaryotic Progeny

  • Kim, Jung-Mi;Yun, Suk-Hyun;Park, Seung-Moon;Ko, Han-Gyu;Kim, Dae-Hyuk
    • The Plant Pathology Journal
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    • v.29 no.4
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    • pp.460-464
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    • 2013
  • dsRNA was found in malformed cultures of Lentinula edodes strain FMRI0339, one of the three most popular sawdust cultivated commercial strains of shiitake, and was also found in healthy-looking fruiting bodies and actively growing mycelia. Cloning of the partial genome of the dsRNA revealed the presence of the RdRp sequence of a novel L. edodes mycovirus (LeV), and sequence comparison of the cloned amplicon showed identical sequences sequence to known RNA-dependent RNA polymerase genes of LeV found in strain HKA. The meiotic stability of dsRNA was examined by measuring the ratio of the presence of dsRNA among sexual monokaryotic progeny. More than 40% of the monokaryotic progeny still contained the dsRNA, indicating the persistence of dsRNA during sexual reproduction. Comparing the mycelia growth of monokaryotic progeny suggested that there appeared to be a tendency toward a lower frequency of virus incidence in actively growing progeny.

Why Should We Consider Potential Roles of Oral Bacteria in the Pathogenesis of Sjögren Syndrome?

  • Sung-Ho Chang;Sung-Hwan Park;Mi-La Cho;Youngnim Choi
    • IMMUNE NETWORK
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    • v.22 no.4
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    • pp.32.1-32.20
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    • 2022
  • Sjögren syndrome (SS) is a chronic autoimmune disorder that primarily targets the salivary and lacrimal glands. The pathology of these exocrine glands is characterized by periductal focal lymphocytic infiltrates, and both T cell-mediated tissue injury and autoantibodies that interfere with the secretion process underlie glandular hypofunction. In addition to these adaptive mechanisms, multiple innate immune pathways are dysregulated, particularly in the salivary gland epithelium. Our understanding of the pathogenetic mechanisms of SS has substantially improved during the past decade. In contrast to viral infection, bacterial infection has never been considered in the pathogenesis of SS. In this review, oral dysbiosis associated with SS and evidence for bacterial infection of the salivary glands in SS were reviewed. In addition, the potential contributions of bacterial infection to innate activation of ductal epithelial cells, plasmacytoid dendritic cells, and B cells and to the breach of tolerance via bystander activation of autoreactive T cells and molecular mimicry were discussed. The added roles of bacteria may extend our understanding of the pathogenetic mechanisms and therapeutic approaches for this autoimmune exocrinopathy.

Molecular Pathogenesis of Spinocerebellar Ataxia Type 1 Disease

  • Kang, Seongman;Hong, Sunghoi
    • Molecules and Cells
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    • v.27 no.6
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    • pp.621-627
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    • 2009
  • Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 is associated with an elongated polyglutamine tract in ataxin-1, the SCA1 gene product. As summarized in this review, recent studies have clarified the molecular mechanisms of SCA1 pathogenesis and provided direction for future therapeutic approaches. The nucleus is the subcellular site where misfolded mutant ataxin-1 acts to cause SCA1 disease in the cerebellum. The role of these nuclear aggregates is the subject of intensive study. Additional proteins have been identified, whose conformational alterations occurring through interactions with the polyglutamine tract itself or non-polyglutamine regions in ataxin-1 are the cause of SCA-1 cytotoxicity. Therapeutic hope comes from the observations concerning the reduction of nuclear aggregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.

Transcriptome Analysis of the Barley-Rhynchosporium secalis Interaction

  • Al-Daoude, Antonious;Shoaib, Amina;Al-Shehadah, Eyad;Jawhar, Mohammad;Arabi, Mohammad Imad Eddin
    • The Plant Pathology Journal
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    • v.30 no.4
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    • pp.425-431
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    • 2014
  • Leaf scald caused by the infection of Rhynchosporium secalis, is a worldwide crop disease resulting in significant loss of barley yield. In this study, a systematic sequencing of expressed sequence tags (ESTs) was chosen to obtain a global picture of the assembly of genes involved in pathogenesis. To identify a large number of plant ESTs, which are induced at different time points, an amplified fragment length polymorphism (AFLP) display of complementary DNA (cDNA) was utilized. Transcriptional changes of 140 ESTs were observed, of which 19 have no previously described function. Functional annotation of the transcripts revealed a variety of infection-induced host genes encoding classical pathogenesis-related (PR) or genes that play a role in the signal transduction pathway. The expression analyses by a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) revealed that Rar1 and Rpg4 are defense inducible genes, and were consistent with the cDNA-AFLP data in their expression patterns. Hence, the here presented transcriptomic approach provides novel global catalogue of genes not currently represented in the EST databases.

Current Challenges of Streptococcus Infection and Effective Molecular, Cellular, and Environmental Control Methods in Aquaculture

  • Mishra, Anshuman;Nam, Gyu-Hwi;Gim, Jeong-An;Lee, Hee-Eun;Jo, Ara;Kim, Heui-Soo
    • Molecules and Cells
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    • v.41 no.6
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    • pp.495-505
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    • 2018
  • Several bacterial etiological agents of streptococcal disease have been associated with fish mortality and serious global economic loss. Bacterial identification based on biochemical, molecular, and phenotypic methods has been routinely used, along with assessment of morphological analyses. Among these, the molecular method of 16S rRNA sequencing is reliable, but presently, advanced genomics are preferred over other traditional identification methodologies. This review highlights the geographical variation in strains, their relatedness, as well as the complexity of diagnosis, pathogenesis, and various control methods of streptococcal infections. Several limitations, from diagnosis to control, have been reported, which make prevention and containment of streptococcal disease difficult. In this review, we discuss the challenges in diagnosis, pathogenesis, and control methods and suggest appropriate molecular (comparative genomics), cellular, and environmental solutions from among the best available possibilities.

Inhibition of ER Stress by 2-Aminopurine Treatment Modulates Cardiomyopathy in a Murine Chronic Chagas Disease Model

  • Ayyappan, Janeesh Plakkal;lizardo, Kezia;Wang, Sean;Yurkow, Edward;Nagajyothi, Jyothi F
    • Biomolecules & Therapeutics
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    • v.27 no.4
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    • pp.386-394
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    • 2019
  • Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.